Scripps Research chemists develop new method for making gamma chiral centers on simple carboxylic acids C-H activation-based method should speed drug molecule design and diversification.
May 17, 2024
LA JOLLA, CA Scripps Research chemists have accomplished a long elusive feat in synthetic chemistry: the invention of a broadly useful method for constructing gamma chiral centers on simple starting compounds called carboxylic acids. The method, published on May 16, 2024 in Science, significantly extends the ability of chemists to build and modify complex pharmaceutical molecules and other valuable chemical products.
The term chiral refers to a type of asymmetry that allows some chemical compounds to exist in left-handed and right-handed forms. Often, only one of these forms has the desired biochemical activity, but for synthetic chemists, stereoselective reactions those that yield just the desired form are almost always challenging.
The new method enables what had been impossible except in narrow cases: creating a center of chiral asymmetry at a hard-to-reach position called the gamma position on a cyclic carboxylic acid.
This approach offers unprecedented and relatively easy access to a broad set of chiral carbocycles that are privileged structures for pharma industry drug discovery programs, says study senior author Jin-Quan Yu, PhD, Frank and Bertha Hupp Professor of Chemistry and Bristol Myers Squibb Endowed Chair in Chemistry at Scripps Research.
The co-first authors were Tao Zhang, PhD, and Zi-Yu Zhang, PhD, both postdoctoral research associates in the Yu lab.
A potentially valuable but elusive method
The development of small molecule pharmaceuticals or other chemical products typically involves the construction of many hundreds or thousands of compounds, each representing a variation on a central structural theme. Once these libraries of compounds are constructed, they are methodically tested for the desired biological or chemical activity; in this way, developers can zero in on the best compound for further refinement. Naturally, in constructing these libraries and in making more refined variants, chemists would like to have easy and versatile techniques for building and modifying molecules. But while their tools have greatly improved over the years, some types of molecular transformation have remained essentially undoable, despite the obvious value they would have. Gamma chiral center construction using readily available carboxylic acids has been one of these, defying the efforts of prominent synthetic chemistry labs.
The Yu lab's success hinged on the development of special ligand molecules containing both oxazoline and pyridone structural elements. Ligand molecules help bring the reaction catalyst to the right spot on the initial compound. In this case, they fasten to one point on the starting carboxylic acid which contains a ring of mostly carbon atoms and direct a bond-breaking palladium atom to the distant gamma position on the other side of the ring. The effect is to remove a hydrogen atom from the backbone carbon atom at the targeted spot, allowing a new cluster of atoms to bond to the carbon thus adding complexity to the molecule in a precise way.
This type of reaction is called a C-H activation, and over the past decade, Yu and his team have reported similar C-H activation methods for constructing chiral centers at alpha and beta positions on carboxylic acids.
The chemists demonstrated the power and versatility of their new method by using it to make gamma chiral centers on a wide variety of relatively simple carboxylic acid starting compounds containing rings of from five to eight carbon atoms. In one case, they achieved a single-step synthesis of a chiral version of a cancer drug molecule called an HDAC inhibitor whose standard, patented synthesis method requires 10 steps and a costly separation to obtain pure samples of the left-handed or right-handed form.
The team also used the new technique to add complexity to existing drug molecules, including the steroid hormone pregnenolone.
Finally, the chemists showed they could use their new approach sequentially on a starting molecule to construct three chiral centers including a very challenging delta chiral center.
The Yu lab is now working to extend the new approach so it can be used for making other types of chiral molecules.
Enantioselective Remote Methylene C H (Hetero)Arylation of Cycloalkane Carboxylic Acids was co-authored by Tao Zhang, Zi-Yu Zhang, Guowei Kang, Tao Sheng, Jie-Lun Yan, Yuan-Bin Yang, Yuxin Ouyang and Jin-Quan Yu, all of Scripps Research.
Support for the research was provided by the National Institutes of Health (2R01GM084019).
Chemistry Yu, Jin-Quan
North America Stories
04/06/2026
Sony Electronics is introducing the SRG-AS10, a 4K 60p-compatible PTZ auto-frami...
04/06/2026
This recent grad from Spring, TX, led creative-video output for the Aggies' men's basketball team last season and has been producing video and creating ...
04/06/2026
For the first time at a women's golf major, every player in the field will r...
04/06/2026
Three Panasonic PT-RQ45 40,000-lumen 3-Chip DLP projectors made their first live...
04/06/2026
Bitmovin and Akamai have announced a collaboration with NRJ Group, a French mult...
04/06/2026
Telestream will exhibit at InfoComm 2026 (Booth N7952), demonstrating media work...
04/06/2026
Sony has announced the development of RIALTO 65, a 65mm format image sensor block for the VENICE 2 digital cinema camera, targeting release in the first half of...
04/06/2026
KOKUSAI DENKI Electric America will exhibit at InfoComm 2026 (Booth N8025, June ...
04/06/2026
Bell Media's TSN and RDS are the exclusive Canadian broadcasters of FIFA Wor...
04/06/2026
The Challenge: Receiving Heavy Media Files From Road Games Quickly and ReliablyT...
04/06/2026
MASV, a managed file transfer platform used in broadcast and live sports product...
04/06/2026
NESN has announced the appointment of Fahad Haider as Vice President of Operations and Engineering. Haider returns to NESN, where he previously served as Vice P...
04/06/2026
David J. Halberstam, who spent almost 50 years in sports as a broadcaster and an executive, died June 2 after a years-long battle with brain cancer.
Over his l...
04/06/2026
Although collegiate production programs are tasked with delivering high-quality ...
04/06/2026
California studio, two production trucks, global distribution system are combine...
04/06/2026
New global program empowers and supports storytellers through scriptwriting course and access to industry experts
TikTok and Sundance Institute today announce...
04/06/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
04/06/2026
Bitmovin, a leading provider of video streaming infrastructure, and Akamai, the cybersecurity and cloud computing company that powers and protects business onli...
04/06/2026
American Underground (AU), the Startup Hub of the South and a community of mor...
04/06/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
04/06/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
04/06/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
04/06/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
04/06/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
04/06/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
04/06/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
04/06/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
04/06/2026
NVIDIA and Microsoft Reinvent Windows PCs for the Age of Personal AI
Brie Clayton June 3, 2026
0 Comments
RTX Spark - a 1-Petaflop Superchip, the Full...
04/06/2026
Inside the Peaky Blinders: The Immortal Man Grade
Brie Clayton June 3, 2026
0 Comments
Simone Grattarola discusses shaping the look in DaVinci Resolve...
04/06/2026
Cine Gear Expo Announces 2026 Awards of Excellence Recipients
Brie Clayton June 3, 2026
0 Comments
Ed Lachman ASC, Caleb Deschanel ASC, and M. David M...
04/06/2026
St. Vincents Live with Orchestra Tour to Feature Berklee Alum Ruby Plume Berklee alumni St. Vincent and Ruby Plume will appear on the same bill across seven d...
04/06/2026
Back to All News
All the Truth in My Lies Coming to Netflix on August 28
Entertainment
04 June 2026
GlobalSpain
Link copied to clipboard
Download the imag...
04/06/2026
Back to All News
Larry Tanz, VP of Content, EMEA, Delivers a Keynote Speech at ...
04/06/2026
Back to All News
Turn Your Living Room into a Stadium With the New FIFA World ...
04/06/2026
Keeping conversations real on LinkedIn Published on Jun 4, 2026 Categories: Product News
LinkedIn Corporate Communications
Share
LinkedIn
Facebook ...
04/06/2026
June's forecast with GeForce NOW: 100% chance of gaming.
GeForce NOW is lining up new adventures for the month, from big-name blockbusters to quirky indies...
03/06/2026
SES and Viva, Mexico's ultra low-cost airline, have launched multi-orbit satellite inflight connectivity on Viva's Airbus aircraft. A total of 60 A320s ...
03/06/2026
The College Football Playoff, ESPN, and TNT Sports have announced kick times and...
03/06/2026
RED Digital Cinema will exhibit at Cine Gear Expo 2026 (Booth 33, June 5-6, Universal Studios Lot), hosting three panels and hands-on product demonstrations.
P...
03/06/2026
Roku has announced the Soccer Zone, a dedicated hub for FIFA World Cup 2026 content available across the United States, Canada, Mexico, Brazil, Colombia, Argent...
03/06/2026
Liverpool FC and Wasabi Technologies have announced a multi-year extension of their partnership, with Wasabi continuing as the club's official cloud storage...
03/06/2026
Grass Valley has announced that Australian News Channel (ANC), operator of Sky News Australia, has deployed Grass Valley AMPP as part of the relocation of its n...
03/06/2026
The Riedel Group has announced the appointment of Gudrun Scharler as CEO of Riedel Networks. She succeeds Michael Martens, who has led Riedel Networks since 201...
03/06/2026
Clear-Com has announced the deployment of its intercom solutions at Itaka Arena ...
03/06/2026
Scott Coker has announced six senior executive appointments for his new global MMA promotion, which launched earlier this year with $60 million in financing. Ad...
03/06/2026
Telemundo, the exclusive Spanish-language home of the FIFA World Cup 2026, has announced its digital and social media programming for the tournament, running Ju...
03/06/2026
The Bundesliga has announced the launch of Captain, an AI assistant built into t...
03/06/2026
Anthony James Partners (AJP) is serving as technology consultant for a moderniza...
03/06/2026
Audio-Technica has announced the recipients of its annual sales rep firm awards for the 2025-26 fiscal year. The awards were presented by Jim Schanz, Executive ...
Scripps Research chemists develop new method for making gamma chiral centers on simple carboxylic acids C-H activation-based method should speed drug molecule design and diversification.
